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Cloning and expression of the mouse histamine H 3 receptor: evidence for multiple isoforms
Author(s) -
Rouleau Agnès,
Héron Anne,
Cochois Véronique,
Pillot Catherine,
Schwartz JeanCharles,
Arrang JeanMichel
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02606.x
Subject(s) - gene isoform , thioperamide , biology , microbiology and biotechnology , receptor , in situ hybridization , alternative splicing , complementary dna , expression cloning , receptor expression , 5 ht5a receptor , histamine h3 receptor , messenger rna , biochemistry , gene , antagonist
The existence of mouse H 3 ‐receptor isoforms was investigated by PCR analysis and cDNA cloning. Splicing mechanisms previously reported in various species are conserved in the mouse. The retention/deletion of a fragment in the third intracellular loop of the mouse receptor leads to the existence of three isoforms designated mH 3(445) , mH 3(413) and mH 3(397) according to the length of their deduced amino acid sequence. PCR analysis showed that mouse H 3 ‐receptor isoforms display different expression patterns in the brain. Following expression in Cos‐1 cells, [ 125 I]iodoproxyfan binding indicated similar pharmacological profiles of the mH 3(445) , mH 3(413) and mH 3(397) isoforms. The pharmacological profile of the mouse H 3 receptor is more similar to the rat receptor than to the human receptor, although some differences were also observed between the mouse and rat receptors. For example, the potency of thioperamide and ciproxifan is slightly higher at the mouse receptor than at the rat receptor but 40–100‐fold higher than at the human receptor. In situ hybridization histochemistry showed that the distribution of H 3 ‐receptor mRNAs in the mouse brain is rather similar to that previously reported in the rat brain. However, the autoradiographic and cellular expression patterns observed in several brain areas such as the thalamus or hippocampus reveal important differences between the two species.